Malignant salivary gland tumors of the tongue: A multicenter REFCOR study.

Salivary carcinomas of minor salivary glands are very infrequent tumors. When located in the tongue, the therapeutic strategy may comprise upfront surgery, which may be debilitating, and/or (chemo-)radiotherapy. The aim of this study was to identify the prognostic factors of salivary carcinomas of the tongue in a population-based cohort. This retrospective multicentric study, based on the "Réseau d'Expertise Français sur les Cancers ORL Rares" (REFCOR), included all the patients with a salivary carcinoma of the tongue, diagnosed between January 2009 and December 2018. Dubious slides were reviewed by REFCOR expert pathologists to ensure diagnostic accuracy. Treatment was performed in accordance with national REFCOR recommendations. From 28 centers, 103 patients were included in this study. Median age at diagnosis was 63 years, and 60.2% were female. Tumors were adenoid cystic carcinomas (41.7%), mucoepidermoid carcinomas (30.1%), and other adenocarcinomas (28.2%). Primary treatment was surgical for 61.2% of them. Five-year overall survival (OS) and event-free survival (EFS) rates were 84.7% and 38.6%, respectively. In multivariable analysis, EFS was significantly worse in case of nonsurgical treatment, alcohol consumption, and glossotonsillar sulcus involvement. N-positive status was the only significant prognostic factor for OS in multivariable analysis. Salivary carcinomas of the tongue represent a heterogeneous group of rare tumors, with a high risk of recurrence. In this national cohort, surgery was associated with better EFS and N-status was the main independent prognostic factor for OS.

Dynamic profiling of immune microenvironment during anti-PD-1 immunotherapy for head and neck squamous cell carcinoma: the IPRICE study.

BACKGROUND: Immune checkpoint inhibitors of programmed cell death protein 1 (PD-1) represent a significant breakthrough in treating head and neck squamous cell carcinoma (HNSCC), with long-lasting responses and prolonged survival observed in first- and second-line therapy. However, this is observed in < 20% of patients and high primary/secondary resistance may occur. The primary objective of the identification of predictive factors for the response to anti-PD-1 immunotherapy in head and neck squamous cell carcinoma (IPRICE) study is to identify predictive factors of response to anti-PD-1 immunotherapy. METHODS: The IPRICE study is a single-center, prospective, non-randomized, open-label, and interventional clinical trial. Liquid and tumor biopsies will be performed in 54 patients with recurrent/metastatic (R/M) HNSCC undergoing anti-PD-1 immunotherapy alone to compare the evolution of gene expression and immunological profile between responders and non-responders. We will use a multidisciplinary approach including spatial transcriptomics, single seq-RNA analysis, clinical data, and medical images. Genes, pathways, and transcription factors potentially involved in the immune response will also be analyzed, including genes involved in the interferon-gamma (IFN-γ) pathway, immunogenic cell death and mitophagy, hypoxia, circulating miRNA-mediated immunomodulation, cytokines, and immune repertoire within the tumor microenvironment (TME). With a follow-up period of 3-years, these data will help generate effective biomarkers to define optimal therapeutic strategy and new immunomodulatory agents based on a better understanding of primary/secondary resistance mechanisms. Tumor biopsy will be performed initially before the start of immunotherapy at the first tumor assessment and is only proposed at tumor progression. Clinical data will be collected using a dedicated Case Report Form (CRF). DISCUSSION: Identifying predictive factors of the response to anti-PD-1 immunotherapy and optimizing long-term immune response require a thorough understanding of the intrinsic and acquired resistance to immunotherapy. To achieve this, dynamic profiling of TME during anti-PD-1 immunotherapy based on analysis of tumor biopsy samples is critical. This will be accomplished through the anatomical localization of HNSCC, which will allow for the analysis of multiple biopsies during treatment and the emergence of breakthrough technologies including single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics. TRIAL REGISTRATION: Clinicaltrial.gov. Registered April 14, 2022, https://www. CLINICALTRIALS: gov/study/NCT05328024 .

Diffusion-weighted and gadolinium-enhanced dynamic MRI in parotid gland tumors.

PURPOSE: To evaluate the value of diffusion-weighted imaging and dynamic contrast-enhanced MRI for the diagnosis of parotid gland tumors. METHODS: Retrospective review of patients with surgically treated parotid tumors between January 2009 and June 2020, who underwent a preoperative parotid gland MRI including standard morphological sequences, diffusion-weighted echoplanar imaging with apparent diffusion coefficient measurement and T1-weighted gadolinium-enhanced dynamic MRI sequences with Fat Saturation. The lesion was classified between malignant vs benign and precisions regarding its histological type were given when possible. Imaging findings were compared with pathology results. RESULTS: Inclusion of 133 patients (mean age: 53 years). Multiparametric MRI had a sensitivity of 90.3%, a specificity of 77.5%, an overall accuracy of 80.5%, a positive predictive value of 54.9% and a negative predictive value of 96.3% to differentiate benign parotid tumor from malignant ones. Specificity (85.5%) and positive predictive value (67.6%) were improved for cases, where anatomical and functional MRI characteristics were conclusive and consistent with clinical findings. CONCLUSIONS: Combining diffusion-weighted and gadolinium-enhanced dynamic sequences, in addition to morphological ones enables high (> 90%) sensitivity to detect malignant parotid gland tumors. It also gives the possibility to characterize pleomorphic adenomas and Warthin tumors and to avoid fine-needle aspiration in cases of typical imaging presentation and reassuring clinical findings.

Tumor-Suppressive and Immunomodulating Activity of miR-30a-3p and miR-30e-3p in HNSCC Cells and Tumoroids.

Head and neck squamous cell carcinomas (HNSCCs) are heterogeneous tumors, well known for their frequent relapsing nature. To counter recurrence, biomarkers for early diagnosis, prognosis, or treatment response prediction are urgently needed. miRNAs can profoundly impact normal physiology and enhance oncogenesis. Among all of the miRNAs, the miR-30 family is frequently downregulated in HNSCC. Here, we determined how levels of the 3p passenger strands of miR-30a and miR-30e affect tumor behavior and clarified their functional role in LA-HNSCC. In a retrospective study, levels of miR-30a-3p and miR-30e-3p were determined in 110 patients and correlated to overall survival, locoregional relapse, and distant metastasis. miR-30a/e-3p were expressed in HNSCC cell lines and HNSCC patient-derived tumoroids (PDTs) to investigate their effect on tumor cells and their microenvironment. Both miRNAs were found to have a prognosis value since low miR-30a/e-3p expression correlates to adverse prognosis and reduces overall survival. Low expression of miR-30a/e-3p is associated with a shorter time until locoregional relapse and a shorter time until metastasis, respectively. miR-30a/e-3p expression downregulates both TGF-ßR1 and BMPR2 and attenuates the survival and motility of HNSCC. Results were confirmed in PDTs. Finally, secretomes of miR-30a/e-3p-transfected HNSCC activate M1-type macrophages, which exert stronger phagocytic activities toward tumor cells. miR-30a/e-3p expression can discriminate subgroups of LA-HNSCC patients with different prognosis, making them good candidates as prognostic biomarkers. Furthermore, by targeting members of the TGF-ß family and generating an immune-permissive microenvironment, they may emerge as an alternative to anti-TGF-ß drugs to use in combination with immune checkpoint inhibitors.

Airway management during transoral robotic surgery for head and neck cancers: a French GETTEC group survey.

PURPOSE: The aim of the survey was to define the indications for preventive tracheostomy in transoral robotic surgery (TORS) for head and neck cancers. METHODS: From October 2019 to January 2020, an online questionnaire was e-mailed to French surgical ENT teams with considerable experience of the TORS procedure (Gettec group). A descriptive analysis of the answers was performed. RESULTS: Eighteen French surgical teams answered the questionnaire. For 77.8% of the surgical teams, a past history of radiotherapy with residual edema was an indication for prophylactic tracheostomy, and for 88.9%, > 75 mg of antiplatelet medication or anticoagulation treatment was an indication. CONCLUSION: Early preventive tracheostomy during TORS can protect airway from uncommon but potentially life-threatening complications, such as transoral hemorrhage or airway edema. We recommend it in high-risk situations, such as a past history of radiotherapy or antiplatelet therapy associated with large resections. Further studies are needed to establish evidence-based recommendations.

Oral tongue squamous cell carcinomas in young patients according to their smoking status: a GETTEC study.

BACKGROUND: Incidence of oral tongue squamous cell carcinoma (OTSCC) is increasing, especially in young adults, despite decreasing tobacco and alcohol consumption. METHODS: This multicentric retrospective study of 185 young adults with OTSCC (median follow-up 43 months), investigated risk factors, tumour characteristics and oncological outcomes according to the smoking status. RESULTS: Overall, 38% of patients were smokers (S). Non-smokers (NS) were significantly younger than S. Sex ratios were 1.1 for N and 1.8 for S. NS patients were less frequently cannabis or alcohol users than S, but were more likely to have a history of leukoplakia. Second primaries were observed in NS (4.4%) and in S (12.7%). Despite more frequent local relapse in NS (p = 0.018), there was no difference in diagnostic stage and overall survival between groups. CONCLUSION: OTSCC affects differently young S and NS patients suggesting the existence of a specific clinical entity of OTSCC in non-smoking young adults.

Evaluation of the information given to patients undergoing total pharyngolaryngectomy and quality of life: a prospective multicentric study.

BACKGROUND: Providing cancer patients with adequate information is essential to their confidence and satisfaction regarding medical care. The aims of this study were to evaluate the information given to patients undergoing total pharyngolaryngectomy (TPL) as well as the evolution and predictors of patient quality of life (QoL). METHODS: We conducted a prospective multicentric study on patients undergoing TPL for a locally advanced laryngeal/hypopharyngeal cancer. All patients completed the EORTC QLQ-INFO25, QLQ-C30, and QLQ-H&N35 questionnaires, before and after surgery. RESULTS: This study enrolled 46 patients. Between the pre- and post-therapeutic periods, we observed no significant changes in the global QLQ-INFO25 and QLQ-C30 scores. However, we found a significant deterioration in 4 QLQ-INFO25 scales/items and in social functioning, as well as an increase of sense, speech, and social contact problems. N-stage and professional activity were significant predictors of preoperative QLQ-INFO25 scores. Younger age was significantly associated with financial difficulties, whereas professional activity and lower education level were significant predictors of xerostomia and swallowing problems, respectively. CONCLUSION: In patients undergoing TPL, we observed significant changes in QLQ-INFO25 scores between the pre- and post-treatment periods and, particularly, a deterioration of patient satisfaction with the information received. Several clinical factors were identified as significant predictors of QLQ-INFO25 and QoL scores.

Functional or radical surgical treatment of laryngeal chondrosarcoma, analysis of survival and prognostic factors: A REFCOR and NetSarc-ResOs multicenter study of 74 cases.

INTRODUCTION: Laryngeal chondrosarcoma (LCS) is a rare tumor of slow evolution whose treatment is poorly codified. For a long time, a radical treatment by total laryngectomy (TL) was proposed. More recent studies tend to propose a conservative surgical approach of the larynx. The objective of this study was to compare the overall survival (OS) of total laryngectomized patients (TL+) versus non-laryngectomized patients (TL-). The secondary objectives were to analyse the reoperation free survival (RFS), the total laryngectomy free survival (TLFS) and to identify the preoperative factors leading surgeons to propose TL. MATERIALS AND METHODS: A retrospective analysis of prospectively collected incident cases from the REFCOR and NetSarc-ResOs multicenter databases between March 1997 and June 2021 was conducted. A propensity score matching analysis was performed to compare the OS of TL+ and TL-patients. RESULTS: 74 patients were included. After propensity score, the 5-year OS of TL+ and TL-patients was comparable (100 %, p = 1). The 5-year RFS rate was 69.2 % (95 % CI [57.5-83.4]) and the 5-year TLFS was 61.7 % (95 % CI [50.4-75.5]). Cricoid involvement greater than 50 % (HR 3.58; IC 95 % [1.61-7.92] p < 0.001), an ASA score of 3 or 4 (HR 5.07; IC 95 % [1.64-15.67] p = 0.009) and involvement of several cartilages (HR 5.26; IC 95 % [1.17-23.6] p = 0.04) are prognostic factors for TL. Dyspnea caused by the tumour is a prognostic factor for reoperation (HR 2.59; IC 95 % [1.04-6.45] p = 0.03). CONCLUSION: These results demonstrate that conservative treatment should be considered as first-line treatment for laryngeal chondrosarcoma.

Impact of facial nerve resection in parotid cancer abutting the facial nerve without preoperative paralysis: A multicentric propensity score-based analysis.

OBJECTIVES: The management of the facial nerve (FN) is a major issue in parotid cancer, especially when there is no preoperative facial palsy and FN invasion is discovered intraoperatively. The aim of this study was to assess the impact of FN resection in patients with parotid cancer abutting the FN, without pretreatment facial palsy, using a propensity score matching. MATERIALS AND METHODS: Data from all patients treated between 2009 and 2020 for a primary parotid cancer abutting or invading the FN but without pretreatment facial palsy were extracted from the national multicentric REFCOR database. Three different definitions of tumors abutting the FN were used for sensitivity analyses, in a retrospective setting. Propensity score matching was used to assess the impact of FN resection on disease-free survival (DFS), overall survival (OS) and locoregional recurrence-free survival (LRRFS). RESULTS: A total of 163 patients with parotid cancer abutting or invading the FN without pretreatment facial palsy were included. Among them, 99 patients (61 %) underwent FN resection. After overlap weighting and multiple imputation, no benefit of FN resection over preservation was found in terms of OS (HR = 1.21, p = 0.6), DFS (HR = 0.88, p = 0.5) and LRRFS (HR = 0.99, p = 1). Sensitivity analyses revealed similar results, and no significant efficacy was found in the subgroup analyses. CONCLUSION: In this retrospective study with propensity score analysis, FN resection did not improve survival outcomes in patients without preoperative facial palsy treated surgically for a primary parotid cancer abutting the FN. In line with recent guidelines, the results of this study suggest that FN preservation should be considered whenever possible in this specific group of patients.

Carcinomas of the external auditory canal: Management and results: A multicenter REFCOR propensity score matching study.

OBJECTIVES: To analyse prognostic factors and survival outcomes of malignant tumors of the external auditory canal, to investigate the role of regional surgery, and adjuvant radiotherapy in early stages and to investigate the role of surgery in operable T4 stage. SETTING: A retrospective analysis was conducted on all patients prospectively included in the national database of the French Expertize Network for Rare ENT Cancers (REFCOR) from January 2000 to December 2016. PARTICIPANTS: 103 patients from 19 reference centers were included. A propensity score matching analysis was applied to enable comparisons between treatments. MAIN OUTCOMES AND MEASURES: Event-free survival, overall survival and factors of poor prognosis of the cohort were described. The interest of local and regional surgery and postoperative radiotherapy were evaluated. RESULTS: The factors of poor prognosis on event-free survival were immunosuppression (p = 0.002), Karnofsky status less than 90% (p = 0.02), body mass index less than 19 Kg / m2 (p = 0.0009), peripheric facial palsy (p = 0.0016), and positive margin (p = 0.0006). In early stages, locoregional surgery was associated with an increase in event-free survival (p = 0.003, HR = 0.21) versus local surgery alone, while postoperative radiotherapy was not associated with an increase in event-free survival (p = 0.86, HR = 0.91) or overall (p = 0.86, HR = 0.91). In locally advanced stages, locoregional surgery followed by radiotherapy was associated with an increase in event-free survival (p = 0.03, HR = 0.39) and overall (p = 0.02, HR = 0.34) versus chemoradiotherapy alone. CONCLUSION AND RELEVANCE: Regional surgery is recommended for early stages of cancers of the external auditory canal. In operable cases, locoregional surgery followed by radiotherapy is recommended.

A novel ΔNp63-dependent immune mechanism improves prognosis of HPV-related head and neck cancer.

Background: Deconvoluting the heterogenous prognosis of Human Papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OSCC) is crucial for enhancing patient care, given its rapidly increasing incidence in western countries and the adverse side effects of OSCC treatments. Methods: Transcriptomic data from HPV-positive OSCC samples were analyzed using unsupervised hierarchical clustering, and clinical relevance was evaluated using Kaplan-Meier analysis. HPV-positive OSCC cell line models were used in functional analyses and phenotypic assays to assess cell migration and invasion, response to cisplatin, and phagocytosis by macrophages in vitro. Results: We found, by transcriptomic analysis of HPV-positive OSCC samples, a ΔNp63 dependent molecular signature that is associated with patient prognosis. ΔNp63 was found to act as a tumor suppressor in HPV-positive OSCC at multiple levels. It inhibits cell migration and invasion, and favors response to chemotherapy. RNA-Seq analysis uncovered an unexpected regulation of genes, such as DKK3, which are involved in immune response-signalling pathways. In agreement with these observations, we found that ΔNp63 expression levels correlate with an enhanced anti-tumor immune environment in OSCC, and ΔNp63 promotes cancer cell phagocytosis by macrophages through a DKK3/NF-κB-dependent pathway. Conclusion: Our findings are the first comprehensive identification of molecular mechanisms involved in the heterogeneous prognosis of HPV-positive OSCC, paving the way for much-needed biomarkers and targeted treatment.

Blocking EREG/GPX4 Sensitizes Head and Neck Cancer to Cetuximab through Ferroptosis Induction.

(1) Background: Epiregulin (EREG) is a ligand of EGFR and ErB4 involved in the development and the progression of various cancers including head and neck squamous cell carcinoma (HNSCC). Its overexpression in HNSCC is correlated with short overall survival and progression-free survival but predictive of tumors responding to anti-EGFR therapies. Besides tumor cells, macrophages and cancer-associated fibroblasts shed EREG in the tumor microenvironment to support tumor progression and to promote therapy resistance. Although EREG seems to be an interesting therapeutic target, no study has been conducted so far on the consequences of EREG invalidation regarding the behavior and response of HNSCC to anti-EGFR therapies and, more specifically, to cetuximab (CTX); (2) Methods: EREG was silenced in various HNSCC cell lines. The resulting phenotype (growth, clonogenic survival, apoptosis, metabolism, ferroptosis) was assessed in the absence or presence of CTX. The data were confirmed in patient-derived tumoroids; (3) Results: Here, we show that EREG invalidation sensitizes cells to CTX. This is illustrated by the reduction in cell survival, the alteration of cell metabolism associated with mitochondrial dysfunction and the initiation of ferroptosis characterized by lipid peroxidation, iron accumulation and the loss of GPX4. Combining ferroptosis inducers (RSL3 and metformin) with CTX drastically reduces the survival of HNSCC cells but also HNSCC patient-derived tumoroids; (4) Conclusions: The loss of EREG might be considered in clinical settings as a predictive biomarker for patients that might undergo ferroptosis in response to CTX and that might benefit the most from the combination of ferroptosis inducers and CTX.

Management of 80 sinonasal undifferentiated carcinomas. Retrospective multicentre study of the French Network of Rare Head and Neck Cancers (REFCOR).

OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive disease requiring multimodal treatment, and multiple new entities once included in the spectrum of SNUC, such as SWI/SNF-deficient carcinomas, are emerging. We aimed to provide new data regarding the role of chemotherapy and surgery and the prognostic factors of disease-free survival. METHODS: This study was based on data from the REFCOR database and included patients with SNUC treated with curative intent from 2007 to 2021 across 22 centres in France. RESULTS: A total of 80 patients were included in the analysis. Among the entire cohort, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 58% and 63%, respectively. Of 100% of the patients treated with irradiation, 29% underwent surgery, 56% neoadjuvant chemotherapy (82% had either a partial or a complete response) and 76% chemoradiotherapy. No treatment modality was associated with a better OS or DFS, including surgery (p = 0.34). There was a trend for a better DFS for the patients treated with chemotherapy (neoadjuvant or concomitant, p = 0.062). Overall survival at 3 years was 58% for SWI/SNF deficient group and 86% for non deficient group (p = 0.14). The locoregional relapse rate without distant metastases was 21% in the exclusive radiotherapy group and 26% in the surgery group. Grade 3 or higher toxicities concerned 9%, 32% and 29% of patients for surgery, radiotherapy and chemotherapy respectively. CONCLUSION: In the management of localised SNUC among all patients treated with irradiation, surgery yielded no benefit, whereas the addition of chemotherapy tended to improve disease-free survival.

The EXTREME Regimen Associating Cetuximab and Cisplatin Favors Head and Neck Cancer Cell Death and Immunogenicity with the Induction of an Anti-Cancer Immune Response.

(1) Background: The first line of treatment for recurrent/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) has recently evolved with the approval of immunotherapies that target the anti-PD-1 immune checkpoint. However, only about 20% of the patients display a long-lasting objective tumor response. The modulation of cancer cell immunogenicity via a treatment-induced immunogenic cell death is proposed to potentially be able to improve the rate of patients who respond to immune checkpoint blocking immunotherapies. (2) Methods: Using human HNSCC cell line models and a mouse oral cancer syngeneic model, we have analyzed the ability of the EXTREME regimen (combination therapy using the anti-EGFR cetuximab antibody and platinum-based chemotherapy) to modify the immunogenicity of HNSCC cells. (3) Results: We showed that the combination of cetuximab and cisplatin reduces cell growth through both cell cycle inhibition and the induction of apoptotic cell death independently of p53. In addition, different components of the EXTREME regimen were found to induce, to a variable extent, and in a cell-dependent manner, the emission of mediators of immunogenic cell death, including calreticulin, HMGB1, and type I Interferon-responsive chemokines. Interestingly, cetuximab alone or combined with the IC50 dose of cisplatin can induce an antitumor immune response in vivo, but not when combined with a high dose of cisplatin. (4) Conclusions: Our observations suggest that the EXTREME protocol or cetuximab alone are capable, under conditions of moderate apoptosis induction, of eliciting the mobilization of the immune system and an anti-tumor immune response in HNSCC.

Laryngeal dysfunction is prominent in asthmatic women treated by inhaled corticosteroids.

BACKGROUND: Dysphonia is a frequent comorbidity of asthma and has been suggested to be a local side effect of inhaled corticosteroids due to laryngeal candidiasis. We hypothesized that dysphonia in asthmatics was not due to laryngeal organic lesions but to laryngeal dysfunction during phonation (LDP). OBJECTIVE: We compared the frequency of LDP in female asthmatic patients treated with inhaled corticosteroids to female controls. METHODS: We compared 68 asthmatic female patients to 53 female control subjects. Pulmonary function tests were performed and the asthmatic patients classified according to the level of inhaled corticosteroids. Dysphonia was defined as a Vocal Handicap Index ≥18 or GRBAS score ≥2. All patients underwent video laryngo-strobe examination, analyzed blindly and separately by two otolaryngologists, describing mucosal changes, LDP, or Organic lesions linked to Laryngeal Dysfunction during Phonation (OLDP). RESULTS: 66.2% of the asthmatic patients exhibited dysphonia and 11.3% of controls (p < 0.001). No laryngeal candidiasis was found, only 3 patients presented laryngeal mucosa inflammation. LDP was observed in 60.3% of asthmatic patients and 18.9% of controls (p < 0.001), and no difference was found for OLDP (11.8% vs. 13.2%). No association was made between LDP, the dosage of inhaled corticosteroid, and bronchial obstruction. CONCLUSIONS: Asthmatic patients were more dysphonic than control subjects. This phenomenon was not explained by mucosal inflammation, laryngeal candidiasis or OLDP. Asthmatic patients had more LDP than controls. There was no relation between LDP, inhaled corticosteroids dosage or bronchial obstruction. These results change our view of inhaled corticosteroid side effects in female asthmatic patients.

Salvage total glossectomy and total glosso-laryngectomy: Are they worth it? A GETTEC French multicenter study.

BACKGROUND: Salvage total glossectomy (TG) or total glosso-laryngectomy (TGL) remain controversial, as highly morbid procedures. The objective was to describe oncological and functional outcomes after salvage TG or TGL. METHODS: We performed a multicenter retrospective study, including patients with previous neck irradiation undergoing TG or TGL for squamous cell carcinoma involving the base of tongue. RESULTS: We included 42 patients: 27 in the TG group and 15 in the TGL group. For the entire cohort, median OS and DFS were estimated at 19 months (95% IC [14-44]) and 10 months (95% IC [7-13]) respectively, with no difference between the two groups. After a median follow-up of 90 months, 10 patients (24%) were alive and free of disease. Att he end of follow-up, we noted a gastrostomy dependency of 89% and 87 %respectively in the TG and TGL group, and 48% of patients in the TG group had a tracheotomy. CONCLUSION: Although local control is difficult to achieve after salvage TG or TGL, these procedures are associated with acceptable survival and chance of cure for a last-resort situation. TG and TGL can be proposed in selected motivated patients after careful shared decision-making.

Present and future of the labyrinth imaging: Focus on the use of T2-weighted and contrast-enhanced delayed FLAIR (1 h) sequences.

OBJECTIVE: Part of the recent progress in the labyrinth imaging has been made possible by the rise of contrast-free T2-weighted and delayed (1h) FLAIR sequences. The aim of this article is to review evidence for the use of these two sequences to image the inner ear, especially the posterior membranous labyrinth. MATERIAL AND METHODS: We analyzed MRI-based papers (2007-2020)using high-resolution T2-weighted or contrast-enhanced FLAIR (1h) sequences to image the inner ear. RESULTS: T2-weighted sequences (3T MRI)enabled the visualization of the posterior membranous labyrinth with good correlation when compared to corresponding histological slices.Significant progress has been made, especially in terms of scanning time, aiming at reducing it, in order to decrease motions artifacts. The saccule is visible on a 3T MRI without significant motion artifacts. Its shape is ovoid, with a maximum height and width of 1.6 and 1.4 mm, respectively. An enlarged saccule was observed in 84%of patients with unilateral Meniere's disease, in 28%of patients with vestibular schwannomas (VS) and 47%of patients with intralabyrinthine schwannomas. VS obstructing the internal auditory canal caused a decrease of the perilymphatic signal (more moderate decrease in meningiomas) on T2 gradient-echo images. Contrast-enhanced FLAIR sequences are useful to image vestibular/facial neuritis and inflammatory inner ear diseases. CONCLUSION: Precise analysis of the posterior membranous labyrinth, in terms of size, shape and signal intensity, is possible on a 3T MRI using high-resolution gradient-echo T2-weighted sequences. Such sequences are an interesting add-on to delayed (4h30) FLAIR-based protocols for labyrinth imaging.

Risk Factors for Pharyngocutaneous Fistula After Total Pharyngolaryngectomy.

PURPOSE: To evaluate the risk factors of pharyngocutaneous fistula after total pharyngolaryngectomy (TPL) in order to reduce their incidence and propose a perioperative rehabilitation protocol. MATERIALS AND METHODS: This was a multicenter retrospective study based on 456 patients operated for squamous cell carcinoma by total laryngectomy or TPL. Sociodemographic, medical, surgical, carcinologic, and biological risk factors were studied. Reactive C protein was evaluated on post-op day 5. Patients were divided into a learning population and a validation population with patients who underwent surgery between 2006 and 2013 and between 2014 and 2016, respectively. A risk score of occurrence of salivary fistula was developed from the learning population data and then applied on the validation population (temporal validation). OBJECTIVE: To use a preoperative risk score in order to modify practices and reduce the incidence of pharyngocutaneous fistula. RESULTS: Four hundred fifty-six patients were included, 328 in the learning population and 128 in the validation population. The combination of active smoking over 20 pack-years, a history of cervical radiotherapy, mucosal closure in separate stitches instead of running sutures, and the placement of a pedicle flap instead of a free flap led to a maximum risk of post-op pharyngocutaneous fistula after TPL. The risk score was discriminant with an area under the receiver operating characteristic curve of 0.66 (95% confidence interval [CI] = 0.59-0.73) and 0.70 (95% CI = 0.60-0.81) for the learning population and the validation population, respectively. CONCLUSION: A preoperative risk score could be used to reduce the rate of pharyngocutaneous fistula after TPL by removing 1 or more of the 4 identified risk factors.

Weekly Paclitaxel, Carboplatin, and Cetuximab as First-Line Treatment of Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma for Patients Ineligible to Cisplatin-Based Chemotherapy: A Retrospective Monocentric Study in 60 Patients.

OBJECTIVE: For most patients suffering from recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), chemotherapy is the main option after considering surgery and reirradiation. Cetuximab combined with a platinum-fluorouracil regimen (EXTREME) has been the standard of care for over a decade. Nevertheless, a significant number of patients remain unfit for this regimen because of age, severe comorbidities, or poor performance status. The aim of this study is to investigate an alternative regimen with sufficient efficacy and safety. METHODS: We reviewed retrospectively the medical charts of all patients treated with paclitaxel, carboplatin, and cetuximab (PCC) at our institution. Eligibility criteria were as follows: first-line R/M-HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx not suitable for local therapy, cisplatin, and/or 5-FU ineligibility, ECOG-PS: 0-2. PCC consisted of paclitaxel 80 mg/m2, carboplatin AUC 2, and cetuximab at an initial dose of 400 mg/m2 then 250 mg/m2, for 16 weekly administrations followed by cetuximab maintenance for patients for whom a disease control was obtained. The primary endpoint was overall survival (OS), and secondary endpoints were overall response rate (ORR), progression free survival (PFS), and safety. RESULTS: We identified 60 consecutive patients treated with PCC between 2010 and 2016 at our institution. Thirty-one patients (52%) were ECOG-PS 2. Fifty-five patients (92%) were cisplatin ineligible. ORR was 43.3% (95% CI, 30.8-55.8), and disease control rate was 65% (95% CI, 52.9-77.1). With a median follow-up of 35.7 months (IQR 28.6-48.8), median PFS was 5.8 months (95% CI, 4.5-7.2), and median OS was 11.7 months (95% CI, 7.5-14.8). For ECOG-PS 0-1 patients, median OS was 14.8 months (95% CI, 12.2-21.7) while it was only 7.5 months (95%CI: 5.5-12.7) for ECOG-PS 2 patients (p < 0.04). Grades III-IV toxicities occurred in 30 patients (50%). Most toxicities were hematologic. Six patients (10%) had febrile neutropenia. Nonhematologic toxicities were reported such as cutaneous toxicities, neuropathy, infusion-related reactions, or electrolyte disorders. CONCLUSION: The weekly PCC regimen seems to be an interesting option in cisplatin-unfit patients. This study shows favorable PFS and OS when compared with what is achieved with the EXTREME regimen and a high controlled disease rate with predictable and manageable toxicities even in the more fragile population.